Integrative topological analysis of mass spectrometry data reveals molecular features with clinical relevance in esophageal squamous cell carcinoma

Combining MS-based proteomic data with network and topological features of such network would identify more clinically relevant molecules and meaningfully expand the repertoire of proteins derived from MS analysis. The integrative topological indexes representing 95.96% information of seven individual topological measures of node proteins were calculated within a protein-protein interaction (PPI) network, built using 244 differentially expressed proteins (DEPs) identified by iTRAQ 2D-LC-MS/MS. Compared with DEPs, differentially expressed genes (DEGs) and comprehensive features (CFs), structurally dominant nodes (SDNs) based on integrative topological index distribution produced comparable classification performance in three different clinical settings using five independent gene expression data sets. The signature molecules of SDN-based classifier for distinction of early from late clinical TNM stages were enriched in biological traits of protein synthesis, intracellular localization and ribosome biogenesis, which suggests that ribosome biogenesis represents a promising therapeutic target for treating ESCC. In addition, ITGB1 expression selected exclusively by integrative topological measures correlated with clinical stages and prognosis, which was further validated with two independent cohorts of ESCC samples. Thus the integrative topological analysis of PPI networks proposed in this study provides an alternative approach to identify potential biomarkers and therapeutic targets from MS/MS data with functional insights in ESCC

Symptomatic psoriatic dactylitis is associated with ultrasound determined extra-synovial inflammatory features and shorter disease duration

Objectives To explore the link between ultrasonographic features of dactylitis in psoriatic arthritis (PsA) and symptoms, digital tenderness and duration of dactylitis. Methods Forty-eight cases of PsA dactylitis were investigated using high frequency ultrasound (US) both in grey scale (GS) and Power Doppler (PD), evaluating the presence and the degree of flexor tenosynovitis, peri-tendinous oedema, subcutaneous PD, extensor tendon involvement, GS synovitis and intra-articular PD signal (PDS) of the involved digits. Patients were compared according to the presence of local pain and digital tenderness, the duration of dactylitis and the concomitant treatment. Results The presence of pain/tenderness was positively associated with US GS flexor tenosynovitis of grade > 2 (p < 0.001), PD-flexor tenosynovitis (p < 0.001), peri-tendinous oedema (p < 0.001) and subcutaneous PDS (p < 0.001); moreover, it was negatively associated with GS synovitis (p < 0.001) and intra-articular PD (p < 0.001). The same positive and negative association with US findings were found comparing patients with duration of dactylitis shorter or longer than the median (24 weeks) (p < 0.001 for all comparisons). Conclusions Pain and digital tenderness are linked to dactylitis duration and earlier lesions are associated with extra synovial inflammatory changes. These findings suggest a hitherto unappreciated extra synovial basis for symptoms in PsA dactylitis